Sponsored by DuPont Crop Protection
Ligand-gated chloride channels and phenolamine GPCRs as important targets of pest control chemicals
Dr. Yoshihisa Ozoe was born and grew up in Izumo, Shimane Prefecture, which is located in the western part of the main island of Japan. He earned his bachelor’s degree (1974), master’s degree (1976), and doctorate (1982) in agricultural chemistry from Kyushu University, Japan. He became assistant professor of environmental chemistry in 1976 and associate professor of bioresource chemistry in 1989 at Shimane University. He is professor of life science and biotechnology at Shimane University from 1996, where he served as department chair for four years.
Dr. Ozoe began his research career by synthesizing insecticidal compounds in the pesticide chemistry laboratory under the supervision of Professor Morifusa Eto where he had the opportunity to study the mode of action of toxic bicyclophosphates. He synthesized the tert-butyl analog in 1976 and found that this type of compounds inhibits spontaneous discharges in the GABAergic neuro-muscular junction of the earthworm. After receiving a doctoral degree, he joined Dr. Fumio Matsumura’s group as a research associate at Pesticide Research Center, Michigan State University (1982 – 1984). He engaged in synthetic work on picrotoxinin/cyclodiene hybrid compounds to support Dr. Matsumura’s notable discovery that cyclodiene insecticides act as GABA receptor antagonists. Dr. Ozoe also worked as a visiting associate professor in Dr. Matsumura’s laboratory at University of California-Davis in 1991 to clone genes encoding insect GABA receptor subunits.
Dr. Ozoe has mainly been studying the modes of action and the structure-activity relationships of insecticidal compounds. His major focus of research is on insect and nematode ligand-gated ion channels as targets of pest control chemicals. While synthesizing noncompetitive antagonists (NCAs) of GABA receptors, he found that structurally diverse NCAs act at the same site and that some of them are selective to insect receptors. He characterized the NCA binding site and showed that the receptor selectivity of NCAs can be changed by their structural modifications. He also indicated that novel chemical types of NCAs, isoxazolines and benzamides, bind to an allosteric site(s) different from the site for conventional NCAs in insect GABA receptors. He recently investigated the actions of competitive antagonists on insect GABA receptors and demonstrated that the orthosteric site is a potential binding pocket for insecticides. His group achieved the cloning, heterologous expression, and characterization of several insect GABA and glutamate receptors as targets of insecticides.
Dr. Ozoe’s research focus is also on G protein-coupled receptors (GPCRs) as targets of insecticides. To study the molecular pharmacology of biogenic amine GPCRs, his group cloned cDNAs encoding two types of octopamine receptors and two types of tyramine receptors from the silkworm. The signaling pathways of insect phenolamine GPCRs and the pharmacology of formamidine insecticides/acaricides were made clearer by these studies.
Dr. Ozoe has made important contributions to the understanding of the mode of action and the selectivity of GABA receptor antagonists to lead to the development of novel insecticides. His GPCR researches enhanced our understanding of the molecular mechanisms of action of octopamine receptor agonist insecticides. He was the recipient of the High-Prospectiveness Award (1985) and the Prominent-Achievement Award (2004) from the Pesticide Science Society of Japan and the Kitaji Mochizuki Award (2004) from Biosafety Research Center, Japan.